Abstract
BackgroundArtemisinin resistance, linked to polymorphisms in the Kelch gene on chromosome 13 of Plasmodium falciparum (k13), has outpaced containment efforts in South East Asia. For national malaria control programmes in the region, it is important to establish a surveillance system which includes monitoring for k13 polymorphisms associated with the clinical phenotype.MethodsBetween February and December 2013, parasite clearance was assessed in 35 patients with uncomplicated P. falciparum treated with artesunate monotherapy followed by 3-day ACT in an isolated area on the Myanmar–Thai border with relatively low artemisinin drug pressure. Molecular testing for k13 mutations was performed on dry blood spots collected on admission.ResultsThe proportion of k13 mutations in these patients was 41.7%, and only 5 alleles were detected: C580Y, I205T, M476I, R561H, and F446I. Of these, F446I was the most common, and was associated with a longer parasite clearance half-life (median) 4.1 (min–max 2.3–6.7) hours compared to 2.5 (min–max 1.6–8.7) in wildtype (p = 0·01). The prevalence of k13 mutant parasites was much lower than the proportion of k13 mutants detected 200 km south in a much less remote setting where the prevalence of k13 mutants was 84% with 15 distinct alleles in 2013 of which C580Y predominated.ConclusionsThis study provides evidence of artemisinin resistance in a remote part of eastern Myanmar. The prevalence of k13 mutations as well as allele diversity varies considerably across short distances, presumably because of historical patterns of artemisinin use and population movements.
Highlights
Artemisinin resistance, linked to polymorphisms in the Kelch gene on chromosome 13 of Plasmodium falciparum (k13), has outpaced containment efforts in South East Asia
The C580Y allele found on the Myanmar–China border appears to have originated from the Thailand–Myanmar border [17]; indicating that genetic mutations associated with artemisinin resistance in P. falciparum are emerging “de novo” in different locations and spreading contiguously
Study site and study design This was an open label non-randomized trial designed to evaluate the association between the efficacy of artemisinin against P. falciparum malaria and k13 mutations using the same protocol as a larger multicentre trial [7]
Summary
Artemisinin resistance, linked to polymorphisms in the Kelch gene on chromosome 13 of Plasmodium falciparum (k13), has outpaced containment efforts in South East Asia. Resistance to the artemisinin derivatives in Plasmodium falciparum, characterized by delayed parasite clearance in patients treated with artesunate, emerged in Western Cambodia in 2007 [1,2,3]. This phenotypic trait was Bonnington et al Malar J (2017) 16:480 mutations have been found, the distribution of different alleles has been variable. The C580Y allele found on the Myanmar–China border appears to have originated from the Thailand–Myanmar border [17]; indicating that genetic mutations (at least C580Y) associated with artemisinin resistance in P. falciparum are emerging “de novo” in different locations and spreading contiguously
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